Synlett 2006(9): 1323-1326  
DOI: 10.1055/s-2006-941575
LETTER
© Georg Thieme Verlag Stuttgart · New York

Enantioselective Formal Synthesis of Brefeldin A and Analogues via Anionic Cyclization of an Alkenyl Epoxide

Tina Hübscher, Günter Helmchen*
Organisch-Chemisches Institut, Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
Fax: +49(6221)544205; e-Mail: G.Helmchen@oci.uni-heidelberg.de;
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Publikationsverlauf

Received 24 February 2006
Publikationsdatum:
22. Mai 2006 (online)

Abstract

Cyclopentene derivatives suitable as intermediates for syntheses of brefeldin A and analogues 6,7-dehydrobrefeldin C and norbrefeldin A were prepared by epoxynitrile cyclization of alkenyl epoxides.

17

The cyclopropane 9 was formed as a mixture of two diastereomers. In the reaction according to entry 1 of Table [1] , the ratio of the diastereomers was 1.5:1 (1H NMR). The configurations of these compounds were not determined.

18

Typical Procedure. A 1 M solution of LHMDS (13.0 mL, 13.0 mmol) in THF was placed in a dry Schlenk tube under argon and the solvent was removed in vacuo. The residue was dissolved in dry DMA (120 mL) at r.t., and a solution of 6a (1.50 g, 6.17 mmol) in dry DMA (50 mL) was added dropwise via syringe pump. The reaction mixture was stirred for 20-60 min, cooled to 0 °C and then treated with sat. aq NH4Cl and Et2O. The aqueous layer was separated, acidified with 1 N aq HCl and extracted with Et2O. The organic layers were washed with 1 N aq HCl, H2O and brine. The combined organic layers were dried over Na2SO4, filtered and evaporated in vacuo. The residue was subjected to flash chromatography on silica gel (120 g, PE-EtOAc 4:1 → 1:1) to give 8a (1.01 g, 67%) as a yellow oil.